Page last updated: 2024-12-10

pd 123319

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

PD123319 : An imidazopyridine consisting of 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine having 4-(dimethylamino)-3-methylbenzyl, diphenylacetyl and carboxy and groups at positions 1, 5 and 6 respectively [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID5311345
CHEMBL ID157946
CHEMBL ID321820
CHEBI ID61014
SCHEMBL ID668525
MeSH IDM0198503

Synonyms (30)

Synonym
CHEBI:61014 ,
(6s)-1-[4-(dimethylamino)-3-methylbenzyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1h-imidazo[4,5-c]pyridine-6-carboxylic acid
(6s)-1-[(4-dimethylamino-3-methylphenyl)methyl]-5-[2,2-di(phenyl)acetyl]-6,7-dihydro-4h-imidazo[5,4-d]pyridine-6-carboxylic acid
gtpl597
130663-39-7
pd 123319 ,
pd123319
pd-123319
CHEMBL157946 ,
bdbm50282396
(s)-1-(4-dimethylamino-3-methyl-benzyl)-5-diphenylacetyl-4,5,6,7-tetrahydro-1h-imidazo[4,5-c]pyridine-6-carboxylic acid
(6s)-1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(2,2-diphenylacetyl)-6,7-dihydro-4h-imidazo[4,5-c]pyridine-6-carboxylic acid
(s)-1-(4-(dimethylamino)-3-methylbenzyl)-5-(2,2-diphenylacetyl)-4,5,6,7-tetrahydro-1h-imidazo[4,5-c]pyridine-6-carboxylic acid
EPITOPE ID:140138
CHEMBL321820
S7098
CS-1548
HY-10259
SCHEMBL668525
AC-33098
AKOS030526087
SW220127-1
DTXSID80926850
BCP08027
EX-A2290
Q27088258
A13201
1h-imidazo[4,5-c]pyridine-6-carboxylic acid, 1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(2,2-diphenylacetyl)-4,5,6,7-tetrahydro-, (6s)-
CCG-269765
(6s)1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1h-imidazo[4,5-c]pyridine-6-carboxylic acid

Research Excerpts

Treatment

ExcerptReferenceRelevance
"Pretreatment with PD 123319 and [Sar1, Ala8] ANG II blocked the urinary and sodium excretion (10.7 +/- 0.8, 9.8 +/- 0.7 ml, and 67 +/- 13 and 57 +/- 17 micro Eq/120 min, respectively, N = 9), whereas pretreatment with PD 123319 partially blocked the water and sodium intake, and the MAP induced by ANG II administration (2.3 +/- 0.3, 1.1 +/- 0.1 ml, and 12 +/- 3 mmHg, respectively, N = 9-10)."( Interaction between paraventricular nucleus and septal area in the control of physiological responses induced by angiotensin II.
Camargo, LA; Saad, WA; Santos, TA; Simões, S, 2002
)
0.64

Pharmacokinetics

ExcerptReferenceRelevance
" Furthermore, the half-life of Ang II in rats pretreated with saline or losartan was significantly greater than that measured in the other three groups."( Role of AT1 and AT2 receptors in the plasma clearance of angiotensin II.
Brosnihan, KB; Chappell, MC; Ferrario, CM; Iyer, SN, 1998
)
0.3

Bioavailability

ExcerptReferenceRelevance
" These effects appear to be mediated by the restoration of nitric oxide bioavailability and involve a complex interaction of both Mas and AT(2) receptors."( Vasoprotective and atheroprotective effects of angiotensin (1-7) in apolipoprotein E-deficient mice.
Casley, D; Gaspari, TA; Tesanovic, S; Vinh, A; Widdop, RE, 2010
)
0.36
"01), suggesting that angiotensin-(1-9) improved basal NO bioavailability in an angiotensin type 2 receptor-sensitive manner."( Angiotensin-(1-9) attenuates cardiac fibrosis in the stroke-prone spontaneously hypertensive rat via the angiotensin type 2 receptor.
Denby, L; Dominiczak, AF; Douglas, K; Flores-Munoz, M; Graham, D; Nicklin, SA; Work, LM, 2012
)
0.38

Dosage Studied

ExcerptRelevanceReference
" The peptides produced dose-related increases in perfusion pressure, and dose-response curves to all six peptides were parallel."( Analysis of responses to angiotensin peptides in the hindquarters vascular bed of the cat.
Garrison, EA; Kadowitz, PJ; Osei, SY; Santiago, JA, 1995
)
0.29
" Meclofenamate and N omega-nitro-L-arginine methyl ester shifted the dose-response curve for ANG IV to the left in a manner similar to that observed with ANG II and ANG III."( Analysis of responses to ANG IV: effects of PD-123319 and DuP-753 in the pulmonary circulation of the rat.
Feng, CJ; Kadowitz, PJ; Kaye, AD; Nossaman, BD, 1995
)
0.29
" Dose-response curves for both peptides were parallel, and the time-to-peak increase in lobar arterial pressure in response to angiotensin IV and angiotensin II was similar whereas the duration of the response to angiotensin IV was significantly shorter."( Analysis of responses to angiotensin IV in the pulmonary vascular bed of the cat.
Cheng, DY; Dent, EL; DeWitt, BJ; Kadowitz, PJ; Nossaman, BD, 1994
)
0.29
" To this end, we studied dose-response curves of phenylephrine (10(-9) to 10(-5) mol/L) in the presence and absence of losartan (10(-9), 10(-7), and 10(-5) mol/L) in SHR aortic rings."( Losartan reduces phenylephrine constrictor response in aortic rings from spontaneously hypertensive rats. Role of nitric oxide and angiotensin II type 2 receptors.
Cachofeiro, V; Lahera, V; Maeso, R; Muñoz-García, R; Navarro-Cid, J; Rodrigo, E; Ruilope, LM, 1996
)
0.29
", the dose-response curve for angiotensin II was shifted to the right in a parallel manner, whereas the administration of higher doses resulted in nonparallel rightward shifts of the angiotensin II dose-response curves."( Analysis of the effects of candesartan in the mesenteric vascular bed of the cat.
Champion, HC; Kadowitz, PJ, 1997
)
0.3
"1 mumol/L) had no alpha 1-adrenoceptor antagonist effect but altered the mode of action of the alpha 1-adrenoceptor antagonist doxazosin: PD123319 changed doxazosin from a competitive to a non-competitive antagonist, as evidenced by the reduced slope of the dose-response curve for the alpha 1-adrenoceptor agonist phenylephrine."( Effect of angiotensin II receptor blockade on the interaction between enalaprilat and doxazosin in rat tail arteries.
Marwood, JF,
)
0.13
" At the lowest dose studied (20 microgram/kg iv), the inhibitory effects of candesartan were competitive, whereas at the highest dose (100 microgram/kg iv) the dose-response curve for angiotensin II was shifted to the right in a nonparallel manner with inhibitory effects that could not be surmounted."( Role of AT(1) receptors and autonomic nervous system in mediating acute pressor responses to ANG II in anesthetized mice.
Bivalacqua, TJ; Champion, HC; Dalal, A; Kadowitz, PJ, 1999
)
0.3
" Uterine ANG II dose-response curves were repeated following administration of the ANG II type 2 receptor (AT(2)) antagonist PD-123319 and then repeated again in the presence of an ANG II type 1 receptor (AT(1)) antagonist L-158809."( Functional role of angiotensin II type 1 and 2 receptors in regulation of uterine blood flow in nonpregnant sheep.
Clark, KE; Greenberg, SG; Lambers, DS, 2000
)
0.31
" Dose-response curves for drinking response to intracerebroventricular injections of ANG II were compared between SD and TG rats."( Glial angiotensinogen regulates brain angiotensin II receptors in transgenic rats TGR(ASrAOGEN).
Bader, M; Böhm, M; Bricca, G; Ganten, D; Monti, J; Schinke, M, 2001
)
0.31
" However, all ARBs caused less than maximal inhibition after the highest dose, thus causing a U-shaped dose-response curve with respect to sympatho-inhibition."( Involvement of the AT(2)-receptor in angiotensin II-induced facilitation of sympathetic neurotransmission.
Balt, JC; Mathy, MJ; Nap, A; Pfaffendorf, M; van Zwieten, PA, 2002
)
0.31
" Dose-response of Ang-I induced a similar contraction of MRA from NT and HT mice, which was increased after endothelium removal."( Role of ACE/AT2R complex in the control of mesenteric resistance artery contraction induced by ACE/AT1R complex activation in response to Ang I.
Boulares, H; Matrougui, K; Palen, DI; Su, J, 2008
)
0.35
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
vasoconstrictor agentDrug used to cause constriction of the blood vessels.
endothelin receptor antagonistA hormone antagonist that blocks endothelin receptors.
angiotensin receptor antagonistA hormone antagonist that blocks angiotensin receptors.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
imidazopyridine
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (5)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Type-1A angiotensin II receptor Rattus norvegicus (Norway rat)IC50 (µMol)0.21000.00040.15553.8000AID39206
Type-1B angiotensin II receptorRattus norvegicus (Norway rat)IC50 (µMol)0.21000.00040.13343.8000AID39206
Type-1 angiotensin II receptorHomo sapiens (human)Ki0.01200.00020.18374.7000AID1560688
Type-2 angiotensin II receptorRattus norvegicus (Norway rat)IC50 (µMol)0.21000.00100.39573.3000AID39206
Type-2 angiotensin II receptorHomo sapiens (human)Ki120.00000.00020.56507.7790AID1560689
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (50)

Processvia Protein(s)Taxonomy
regulation of cell growthType-1 angiotensin II receptorHomo sapiens (human)
kidney developmentType-1 angiotensin II receptorHomo sapiens (human)
renin-angiotensin regulation of aldosterone productionType-1 angiotensin II receptorHomo sapiens (human)
maintenance of blood vessel diameter homeostasis by renin-angiotensinType-1 angiotensin II receptorHomo sapiens (human)
regulation of systemic arterial blood pressure by renin-angiotensinType-1 angiotensin II receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayType-1 angiotensin II receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayType-1 angiotensin II receptorHomo sapiens (human)
positive regulation of cytosolic calcium ion concentrationType-1 angiotensin II receptorHomo sapiens (human)
Rho protein signal transductionType-1 angiotensin II receptorHomo sapiens (human)
positive regulation of macrophage derived foam cell differentiationType-1 angiotensin II receptorHomo sapiens (human)
regulation of vasoconstrictionType-1 angiotensin II receptorHomo sapiens (human)
calcium-mediated signalingType-1 angiotensin II receptorHomo sapiens (human)
positive regulation of phospholipase A2 activityType-1 angiotensin II receptorHomo sapiens (human)
low-density lipoprotein particle remodelingType-1 angiotensin II receptorHomo sapiens (human)
regulation of renal sodium excretionType-1 angiotensin II receptorHomo sapiens (human)
angiotensin-activated signaling pathwayType-1 angiotensin II receptorHomo sapiens (human)
regulation of cell population proliferationType-1 angiotensin II receptorHomo sapiens (human)
symbiont entry into host cellType-1 angiotensin II receptorHomo sapiens (human)
regulation of inflammatory responseType-1 angiotensin II receptorHomo sapiens (human)
positive regulation of inflammatory responseType-1 angiotensin II receptorHomo sapiens (human)
positive regulation of protein metabolic processType-1 angiotensin II receptorHomo sapiens (human)
cell chemotaxisType-1 angiotensin II receptorHomo sapiens (human)
phospholipase C-activating angiotensin-activated signaling pathwayType-1 angiotensin II receptorHomo sapiens (human)
blood vessel diameter maintenanceType-1 angiotensin II receptorHomo sapiens (human)
positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesisType-1 angiotensin II receptorHomo sapiens (human)
positive regulation of CoA-transferase activityType-1 angiotensin II receptorHomo sapiens (human)
positive regulation of reactive oxygen species metabolic processType-1 angiotensin II receptorHomo sapiens (human)
inflammatory responseType-1 angiotensin II receptorHomo sapiens (human)
blood vessel remodelingType-2 angiotensin II receptorHomo sapiens (human)
regulation of systemic arterial blood pressure by circulatory renin-angiotensinType-2 angiotensin II receptorHomo sapiens (human)
angiotensin-mediated vasodilation involved in regulation of systemic arterial blood pressureType-2 angiotensin II receptorHomo sapiens (human)
brain renin-angiotensin systemType-2 angiotensin II receptorHomo sapiens (human)
cell surface receptor signaling pathwayType-2 angiotensin II receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayType-2 angiotensin II receptorHomo sapiens (human)
G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messengerType-2 angiotensin II receptorHomo sapiens (human)
brain developmentType-2 angiotensin II receptorHomo sapiens (human)
regulation of blood pressureType-2 angiotensin II receptorHomo sapiens (human)
negative regulation of heart rateType-2 angiotensin II receptorHomo sapiens (human)
negative regulation of cell growthType-2 angiotensin II receptorHomo sapiens (human)
positive regulation of phosphoprotein phosphatase activityType-2 angiotensin II receptorHomo sapiens (human)
regulation of metanephros sizeType-2 angiotensin II receptorHomo sapiens (human)
exploration behaviorType-2 angiotensin II receptorHomo sapiens (human)
nitric oxide-cGMP-mediated signalingType-2 angiotensin II receptorHomo sapiens (human)
angiotensin-activated signaling pathwayType-2 angiotensin II receptorHomo sapiens (human)
vasodilationType-2 angiotensin II receptorHomo sapiens (human)
negative regulation of blood vessel endothelial cell migrationType-2 angiotensin II receptorHomo sapiens (human)
positive regulation of DNA-templated transcriptionType-2 angiotensin II receptorHomo sapiens (human)
negative regulation of neurotrophin TRK receptor signaling pathwayType-2 angiotensin II receptorHomo sapiens (human)
neuron apoptotic processType-2 angiotensin II receptorHomo sapiens (human)
positive regulation of metanephric glomerulus developmentType-2 angiotensin II receptorHomo sapiens (human)
positive regulation of branching involved in ureteric bud morphogenesisType-2 angiotensin II receptorHomo sapiens (human)
positive regulation of extrinsic apoptotic signaling pathwayType-2 angiotensin II receptorHomo sapiens (human)
inflammatory responseType-2 angiotensin II receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (6)

Processvia Protein(s)Taxonomy
angiotensin type I receptor activityType-1 angiotensin II receptorHomo sapiens (human)
angiotensin type II receptor activityType-1 angiotensin II receptorHomo sapiens (human)
protein bindingType-1 angiotensin II receptorHomo sapiens (human)
bradykinin receptor bindingType-1 angiotensin II receptorHomo sapiens (human)
protein heterodimerization activityType-1 angiotensin II receptorHomo sapiens (human)
angiotensin type II receptor activityType-2 angiotensin II receptorHomo sapiens (human)
protein bindingType-2 angiotensin II receptorHomo sapiens (human)
receptor antagonist activityType-2 angiotensin II receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (2)

Processvia Protein(s)Taxonomy
plasma membraneType-1 angiotensin II receptorHomo sapiens (human)
membraneType-1 angiotensin II receptorHomo sapiens (human)
plasma membraneType-1 angiotensin II receptorHomo sapiens (human)
plasma membraneType-2 angiotensin II receptorHomo sapiens (human)
plasma membraneType-2 angiotensin II receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (7)

Assay IDTitleYearJournalArticle
AID1810191Displacement of [125-I]-[Sar1, AngII from AT1R (unknown origin) expressed in Escherichia coli BL 21 (DE3) incubated for 2 hrs by radioimmunoassay2021Journal of medicinal chemistry, 04-08, Volume: 64, Issue:7
Selective Discovery of GPCR Ligands within DNA-Encoded Chemical Libraries Derived from Natural Products: A Case Study on Antagonists of Angiotensin II Type I Receptor.
AID1560688Inhibition of human AT1 receptor2020Journal of medicinal chemistry, 03-12, Volume: 63, Issue:5
The Other Angiotensin II Receptor: AT
AID39206Binding affinity for rat brain Angiotensin II receptor1991Journal of medicinal chemistry, Nov, Volume: 34, Issue:11
Synthesis and structure-activity relationships of a novel series of non-peptide angiotensin II receptor binding inhibitors specific for the AT2 subtype.
AID1560689Inhibition of human AT2 receptor2020Journal of medicinal chemistry, 03-12, Volume: 63, Issue:5
The Other Angiotensin II Receptor: AT
AID39205Binding affinity against Angiotensin II receptor, from rat adrenal gland1991Journal of medicinal chemistry, Nov, Volume: 34, Issue:11
Synthesis and structure-activity relationships of a novel series of non-peptide angiotensin II receptor binding inhibitors specific for the AT2 subtype.
AID1346340Human AT2 receptor (Angiotensin receptors)1990Molecular pharmacology, Sep, Volume: 38, Issue:3
Subclasses of angiotensin II binding sites and their functional significance.
AID1346340Human AT2 receptor (Angiotensin receptors)1991Journal of cardiovascular pharmacology, Feb, Volume: 17, Issue:2
Characterization of distinct angiotensin II binding sites in rat adrenal gland and bovine cerebellum using selective nonpeptide antagonists.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (871)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's289 (33.18)18.2507
2000's371 (42.59)29.6817
2010's203 (23.31)24.3611
2020's8 (0.92)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 19.24

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index19.24 (24.57)
Research Supply Index6.80 (2.92)
Research Growth Index4.40 (4.65)
Search Engine Demand Index23.28 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (19.24)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials6 (0.67%)5.53%
Reviews7 (0.78%)6.00%
Case Studies1 (0.11%)4.05%
Observational0 (0.00%)0.25%
Other880 (98.43%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]